CDMO | Oligonucleotide Development | Custom Oligo Synthesis

Overview of oligonucleotide API development & manufacturing and CDMOs offering custom oligo synthesis, peptide & oligonucleotide development services.

Q1: What are oligonucleotides and polynucleotides?

Oligonucleotides, or oligos, are short single strands of synthetic DNA or RNA that serve as the starting point for many molecular and synthetic biology applications. Oligos are typically between 20-35 bases long and are called primers. Whether it's genetic testing, forensic research, or next-generation sequencing, oligonucleotide often serves as the foundation.

Oligonucleotide APIs are the specific category of oligonucleotides developed as the active pharmaceutical ingredient in therapeutic drugs. These are designed, synthesized, and manufactured under strict regulatory guidelines to meet pharmaceutical standards.

Some characteristics of oligonucleotide APIs are that they are specifically designed to bind to complementary nucleic acid sequences with high precision. Oligonucleotide and peptide APIs are chemically modified to improve their stability, efficacy, and enhanced cellular uptake.

Oligonucleotide APIs offer a promising approach to treat genetic disorders, cancers, and other diseases by specifically targeting and modulating the expression of genes involved in these conditions. Where oligonucleotide APIs can be used for various purposes, including as primers in PCR, probes in DNA sequencing, and as therapeutic agents.

Polynucleotides, on the other hand, are longer chains of nucleotides, forming the structural basis of DNA and RNA. They can consist of hundreds to thousands of nucleotide units and play crucial roles in genetic information storage, transfer, and expression. Polynucleotide API development and manufacturing is essential for leveraging the potential of these molecules.

Polynucleotides are used in drug and gene delivery, biosensing, and barcoding, with various preservation techniques explored to maintain its integrity during delivery. Optimizing polynucleotide API development and manufacturing processes is crucial for meeting safety and efficacy standards.

Additionally, partnering with a CDMO for polynucleotides can help ensure streamlined production and high-quality outcomes. As the demand grows, CDMO for polynucleotides and oligonucleotides plays a crucial role in scaling up development and manufacturing processes while adhering to stringent regulatory requirements.

Q2: What are the challenges faced during the development of oligonucleotide APIs, and how are they addressed?

Oligonucleotide APIs face several challenges during oligonucleotide API custom synthesis and development. These challenges span chemical, manufacturing, regulatory, and logistical aspects, each requiring tailored solutions to ensure successful outcomes. Some of these challenges are mentioned below:

Stability issues faced during development and manufacturing of high-quality oligonucleotides arise because they are susceptible to degradation by nucleases, which can limit its shelf life and efficacy. Modifications like phosphorothioate backbones and 2'-O-methyl groups are commonly used to enhance its stability and specificity.

Maintaining purity standards while development of oligonucleotide APIs is crucial for therapeutic use of oligonucleotide and peptide APIs, requiring effective purification to remove truncated sequences and by-products. While sequence design is straightforward, maintaining purity and yield during scale-up is challenging. To achieve high purity levels, scalable purification methods such as HPLC and ion exchange chromatography are implemented.

Efficient delivery of oligonucleotide drug substances into cells through cell membranes is problematic due to degradation by nucleases, large size and negative charge of oligonucleotides. Using innovative delivery systems such as lipid nanoparticles (LNPs) and conjugation with molecules like GalNAc are used to improve delivery and cellular uptake.

CDMO for oligonucleotide APIs face another layer of complexity i.e. regulatory compliance. Oligonucleotide API manufacturers must meet strict requirements from regulatory agencies, document everything meticulously, and validate their processes extensively. This can be addressed through comprehensive quality management systems and regular audits, ensuring that every step of oligo drugs synthesis to the final product meets the required standards.

Peptides and oligonucleotides continue to evolve as new solutions are sought for efficient development of oligonucleotide APIs and peptide APIs. Challenges in clinical manufacturing of APIs, oligonucleotide APIs custom synthesis and oligo API development, highlight the complexities involved in the manufacturing process. These challenges make the oligonucleotide API development and manufacturing difficult, despite its growing market potential and therapeutic applications.

As this field encompassing oligonucleotide API custom synthesis and oligopolypeptide development continues to evolve, new technologies and approaches are constantly being developed to address these challenges more effectively. For instance, advances in automation and analytical methods are making oligonucleotide development more efficient and reliable. However, successful oligonucleotide APIs contract manufacturing still requires careful consideration and management of all these interconnected challenges.

Q3: What are the key considerations for scaling up oligonucleotide synthesis from laboratory to industrial scale?

Leading pharmaceutical CDMOs (Contract development and manufacturing organization) and CMOs (Contract manufacturing organizations) are instrumental in scaling up oligo contract manufacturing processes from the lab to industrial scale, focusing on optimizing conditions and integrating it into existing manufacturing workflows. During development and manufacturing of high-quality oligonucleotides, scaling up from laboratory to industrial scale it is necessary to ensure these key considerations:

Optimization of reaction conditions: Adjusting temperature conditions during oligonucleotide and peptide API manufacturing and maintaining reagent concentrations is essential to achieve consistent results, allowing for higher yields of oligo drugs in shorter production times.

Automation: Implementing automated synthesis platforms in oligonucleotide APIs custom synthesis enhances the output and reduces the chances of human errors. It can help improve consistency, efficiency and scale-up during oligonucleotide API clinical manufacturing.

Purification techniques: During purification it is necessary to ensure quality for scaling up of APIs. Selecting scalable purification methods in oligo API development, such as HPLC and ion exchange chromatography (IEX) that can be scaled, without affecting the quality of the oligonucleotide output, while accommodating larger production volumes in clinical manufacturing of APIs.

Quality control: Implementing Good Manufacturing Practices (GMP) is essential for maintaining quality during production. Companies provide custom oligo synthesis services following effective quality control protocols to monitor the purity, effectiveness and integrity of oligonucleotides.

Yield optimization: Effective manufacture of oligonucleotide APIs is crucial for achieving yield optimization and productivity. By determining optimal batch sizes during oligo API development that balances efficiency and resource availability, CDMOs can maximize yield at each stage of synthesis and minimize waste.

Regulatory compliance: In oligonucleotide APIs contract manufacturing, ensuring the integrity of the oligonucleotide drug substance, following GMP-compliant API manufacturing and thorough documentation are necessary to ensure quality, regulatory inspections and traceability.

Stability and storage considerations: Developing appropriate storage solutions for final products is essential to maintain stability in oligonucleotide development. Additionally, implementing temperature-controlled storage and transport systems, or cold chain logistics, is vital for preserving sensitive oligonucleotides and polynucleotides throughout the production and distribution processes.

Cost efficiency and economic feasibility: These are critical in the development and manufacturing of high-quality oligonucleotides, particularly when analyzing the cost implications of scaling operations, including materials, labor, and equipment, to ensure financial viability. This includes sourcing high-quality raw materials for oligo contract manufacturing and securing reliable sources for these in sufficient quantities to support large-scale production of oligonucleotide drug substances and peptide APIs.

Risk management: It involves conducting failure mode analysis to identify potential points of failure in the scale-up process and developing contingency plans. Training personnel in large-scale synthesis techniques and equipment operation is also crucial for successful oligonucleotide and peptide API manufacturing.

Environmental considerations: It includes waste management strategies that align with environmental regulations, as well as sustainability practices that incorporate green chemistry approaches to minimize environmental impact.

By addressing these considerations, particularly in the context of oligonucleotide APIs contract manufacturing, oligonucleotide API custom synthesis and clinical manufacturing of APIs, companies can effectively scale up oligonucleotide synthesis while maintaining quality ensuring they remain competitive in the oligonucleotide API landscape and advancing oligopolypeptide development and the production of peptides and oligonucleotides.

Q4: Which are the leading pharmaceutical CDMOs offering oligonucleotide and polynucleotide development?

There are various CDMOs and CMOs that may provide oligonucleotide development, custom oligonucleotide synthesis services and polynucleotide API development and manufacturing for the pharma industry. These CDMOs offering oligonucleotide API development and manufacturing ensure regulatory compliance and high-quality standards, driving innovation in oligonucleotide GMP manufacturing.

Some of the leading pharmaceutical CDMO for oligonucleotide APIs are: -

Anhui Ribobay Pharmaceutical: CDMO for oligonucleotide APIs

Anhui Ribobay Pharmaceutical has expertise in oligonucleotides including siRNA, antisense oligonucleotide APIs, miRNAs, aptamers and oligonucleotides CXOs. Ribobay is a contract research, development, and manufacturing organization (CRDMO) offering GMP-grade oligonucleotide API custom synthesis services across all stages of drug development, from drug screening to commercialization.

EUROAPI: Development of oligonucleotide APIs

EUROAPI is a leading small molecules API player, providing CDMO services for active pharmaceutical ingredients. EUROAPI can provide different classes of Tides using solid-phase chemistry. It is a CDMO for oligonucleotide APIs offering customized manufacturing as well as a full array of development activities for Tides including oligonucleotide GMP manufacturing.

Bachem: Oligonucleotide API manufacturer

Bachem specializes in oligonucleotide and peptide API manufacturing. Bachem has extensive experience in the contract development and manufacturing of peptides and oligonucleotides. It is a CDMO for oligonucleotide APIs that also offers amino acids, complex organic molecules, antisense oligonucleotide APIs and biologically active pharmaceutical ingredients.

Nippon Shokubai: Oligonucleotide API custom synthesis

Nippon Shokubai offers oligonucleotide GMP manufacturing, oligonucleotide API clinical manufacturing and provides custom RNA oligo synthesis, custom DNA oligos, API oligos, DNA, RNA oligonucleotides, and custom oligo synthesis services.

PolyPeptide: CDMO for polynucleotides and oligonucleotides

PolyPeptide is a CDMO, specializing in the contract manufacturing of oligonucleotides, polynucleotides and oligopolypeptide development. With expertise in manufacture of oligonucleotide APIs, PolyPeptide provides custom nucleic acid manufacturing services, including oligo synthesis tailored to the specific needs.

ST Pharma: GMP-compliant API manufacturing

ST Pharma offers oligonucleotide API custom synthesis services. It is a CDMO for oligonucleotide APIs offering synthesis and cGMP manufacturing for API oligos and microRNAs. Its GMP-compliant API manufacturing includes custom oligo drugs, custom DNA oligos, oligonucleotide API clinical manufacturing, and oligonucleotide API development and manufacturing.

STA Pharmaceutical: Oligonucleotide API clinical manufacturing

STA Pharmaceutical’s oligo contract manufacturing platform provides CRDMO services from discovery to commercial scale for drug substances and drug products. Its oligonucleotide API clinical manufacturing platform supports high throughput library synthesis and custom oligo synthesis services (nmol-mmol). With expertise in the manufacture of oligonucleotide API, it also specializes in oligo monomers, linkers, ligands, conjugates and antisense oligonucleotide APIs.

Otsuka Chemical: Oligonucleotide API development and manufacturing

Otsuka Chemical is a CDMO (contract development and manufacturing organization) that provides custom nucleic acid production. Being an oligonucleotide API manufacturer, it offers cGMP oligonucleotide manufacturing services for custom oligos and custom DNA oligonucleotides.

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